SEROSAL PATCH OF THE GASTROESOPHAGEAL JUNCTION: AN EXPERIMENTAL STUDY IN DOGS

SEROSAL PATCH OF THE GASTROESOPHAGEAL JUNCTION. AN EXPERIMENTAL STUDY IN DOGS¹

Paulo Mendelssonh ²

Albino Magalhães ³

Saul Goldenberg ⁴

MENDELSSONH, P.; MAGALHÃES, A.; GOLDENBERG, S. – Serosal patch of the gastroesophageal junction: an experimental study in dogs. Acta Cir. Bras., 13(3):00-00, 1998.

SUMMARY: Thirty two dogs were operated on in order to evaluate the mucosal regeneration of the serosal patch at the gastroesophageal junction. The operation began with a cardiotomy involving one centimeter of the esophagus and two centimeters of the stomach, originating an elliptical serosal surface three centimeters long and one centimeter large. turned to the digestive lumen. The animals were divided into four groups of eight dogs each and named: 1, 2, 3 and 4; they were sacrificed after one, two, four and eight weeks respectively. The results were evaluated by post-operative clinical aspects, macro and microscopic analysis. Post-operative morbidity was low, without signs of digestive tract obstruction. Macroscopically, the patch area at the first week became an ulcerated lesion, with a necrotic bottom; at the second and fourth weeks there was a progressive reduction of the ulcer, from its boundaries to the center, until the complete healing at the eighth week. Microscopically, the serous membrane disappeared early and it was replaced by inflamatory cells and severe neovascular formation, which fitted as a bed to the epithelial proliferation. The neo-epithelization occurred from the periphery to the center of the lesion. At the esophagus this process was completed within two weeks, with multiple layers of cells; at the stomach, within four weeks, with an unicellular epithelium. The corium, showing an inflamatory reaction at the first week, with fibrinoid necrosis and polimorphonuclear cells, changed to a fibroblastic proliferation with mononuclar cells at the second and fourth weeks and, finally, to fibrosis at the eighth week. In the animals sacrificed lately there was regeneration of the smooth muscle layer of the esophagus. At electronic microscopy, the neo-epithelium of the esophagus had all the layer which constitute the normal esophageal epithelium.

SUBJECT HEADINGS: Gastrointestinal surgery. Epithelium.

INTRODUCTION

The surgical treatment of lesions of the gastrointestinal tract has always been a challenge, and various procedures have been described for this; fundic patch operation is one of them.

A great interest in serosal patch procedures began with the management of duodenal ruptures, which were responsible for mortality rates varying from 23% to 55%⁷. KOBOLD and THAL¹⁵ demonstrated successful healing of experimentally induced duodenal injuries by using serosal patch with jejunal loop; their main objective consisted of testing an experimental model for second intention healing of severe duodenal injuries, with avoidance of primary suturing . Following their pioneer study, HATAFUKU and THAL¹¹ applied the technique for experimental serosal patching of the gastroesophageal junction . In 1965, THAL, HATAFUKU and KURTZMAN²⁹ defined experimentally the use of the patch for widening the gastroesophageal junction, with views to the clinical treatment of benign stenoses; they observed rapid healing of the esophageal squamous epithelium on one end of the patch , and of the columnar gastric epithelium on the other end of it, and concluded favorably for the clinical use of the technique.

Based on the above, several authors applied the serosal patch to various other segments of the gastrointestinal tract, such as duodenum⁴,stomach, large and small bowel¹³, as alternative approach to pyloroplasties¹ and in the treatment of the short bowel syndrome⁵.

Clinical application of the method started soon after the first experimental studies, due mainly to the initial successful results: good clinical results were achieved, particularly with the gastroesophageal junction, and the pioneer work was done by THAL and HATAFUKU²⁸, in 1964, using the serosal patch in a case of spontaneous esophageal rupture.

In 1965, THAL ³⁰ reported 16 cases of lower esophageal stenosis, being two with achalasia, three with peptic stenosis, and eleven with hiatus hernia ; In a subsequent paper he reported a larger experience, with 36 patients , describing technical details of the procedure, and proposing the serosal patch as safe and efficient method of treatment in the main surgical challenges of the gastroesophageal junction: peptic stenosis, achalasia and esophageal perforation³¹.

Subsequently to the above reports, a number of authors made clinical use of the technique in cardiac affections such as benign distal esophageal stenosis⁹, achalasia and reflux esophagitis ²⁴, peptic stenosis³², achalasia, perforation and stenosis^16,31, achalasia¹², stenosis due to scleroderma²¹, and severe distal esophageal stenosis¹⁹. Among us (Brazil), the main interest was centered in the treatment of achalasia of the esophagus due to Chagas' disease^{2,3,17,18,20,26,10}. Inspite of a wide clinical application, reported studies of experimental serosal patch of the GE junction are relatively few, and carried out by a single group of authors (THAL and co-workers), with eventual failures occurring certainly due to limited knowledge of biological phenomena undergoing in the process. Based on this, it was deemed appropriate to design and perform an experimental study, with acceptable number of animals, that it would allow observation and analysis of healing at several stages, in order to improve knowledge of his subject.

METHOD

Thirty-two male adult short-haired dogs of indefinite strain, with weights varying from 8 to 14 kg underwent laparotomy, cardiotomy and closure of the GE junction with a gastric serosal patch. At the end of the operative procedure, they were randomly assigned to four groups of eight animals (groups 1 to 4), which were sacrificed at one, two, four and eight weeks after the operation, respectively.

The animals were kept fasting for twenty-four hours before the operation, anesthetised with sodium thiopental 20 mg/kg intravenously, complemented with varying doses (5 to 7 mg/kg) of intravenous ketamin chlorhydrate, and maintained on intermittent positive breathing with the help of endotracheal tube and respirator. An abdominal upper midline incision was performed, the abdomen explored, and after division of the left triangular ligament of the liver, identification and repair of the anterior vagus nerve, and division of the short gastric vessels, the gastric fundus and cardia were mobilised. The cardia was repaired with two 3-O silk sutures and the GE junction was opened longitudinally up to one centimeter proximal and two centimeters distal to the squamocolumnar epithelial junction ( Z line).

Closure of the esophago-gastrotomy opening was done with a continuous 3-O polypropilene suture, starting at the distal end of the incision and running proximally, joining the seromuscular wall of the gastric fundus to the left border of the incision. At the proximal end, the direction of suturing turned and ran towards the distal end, now joining the gastric wall to the right border of the incision. Upon completion of the procedure, it was formed a three centimeters long and one centimeter wide elliptical serosal patch of gastric fundus wall, closing the previously opened lumen.

The abdominal cavity was irrigated with saline and the abdominal wall closed with a running 2-O silk suture . No drains were left in, and no postoperative medication was used. Clear liquids were offered to the dogs in the first 48 hours postoperatively and a full diet afterwards. Feed intake, fecal and urine output were closely observed. Clinical observation was oriented to record the occurrence of vomiting, diarrhea, wound infection, anastomotic leaking and bowel obstruction.

The animals were sacrificed with an intravenous injection of sodium thiopenthal and ether; the lower third of the esophagus, the cardia and the stomach were removed in one block, opened alongside the lesser curvature of the stomach, and conserved in a 10% formalin solution for not less than 48 hours. At laparotomy, occurrence of bowel adherences and obstruction were sought. The removed specimen was carefully examined, before placing it in formalin, in order to record the size of the patch, healing of the mucosa , position of the squamocolumnar junction, and occurrence of necrosis, ulcer, granulation tissue, fistula, foreign body and local infection. Microscopic examinations of the removed specimen were done at three levels of the elliptical patch, labelled esophagus, stomach-1 and stomach-2, sections being taken from the proximal, middle and distal parts of the patch, respectively (Fig. 1). The slides were stained with hematoxylin - eosin and Masson' s trichromic.

Fig. 1.
Sites of specimens obtained for microscopic studies: esophagus, stomach-1, stomach-2.

On microscopy, the analysis was directed to the epithelial and subepithelial appearance of the newly formed mucosa, attributing a plus (+) or a minus (-) sign for the presence or absence of the following variables: serosa, continuity and maturation of the epithelium, focal necrosis, polymorphonuclear leukocytes and mononuclear cells infiltrate, neovascular growth, connective tissue proliferation and fibrosis.

Transmission electron microscopy of a newly formed esophageal epithelium was done in one specimen, obtained from a dog sacrificed at four weeks (group 3). A previous pilot study had shown epithelial maturity at this stage, on optical microscopy. The fresh specimen was placed in a 2% glutaraldehyde solution, and included in resin. Thin sections stained with 1% toluidin blue were examined to define the appropriate site, which was then sliced into ultra thin sections contrasted with an aqueous solution of 3% uranyl acetate and lead citrate.

The variables were analyzed with nonparametric statistical analyses, and the 2 x N chi-square partition test ^8,27, COCHRAN'S G test and Mc NEMAR'S test²⁵ were used. The 5% rejection level was chosen for all tests, and significant values are marked with an asterisk (*).

RESULTS

Wound infection occurred in four animals: two dogs of group 2, and one dog in each of groups 3 and 4. The intake and output were normal in all dogs and neither vomiting, diarrhea nor bowel obstrution occurred.

Adherences of the liver and of the greater omentum to the operative site, at the gastroesophageal junction, were present in all dogs at the time of the sacrifice.There was no evidence of cardioplasty obstruction in any of the specimens removed.

Specimens obtained one week postoperatively (dogs of group 1) presented the patch as a denuded elliptical lesion with irregular borders, having similar measurements as at operation (3 x 1cm), and with surrounding mucosal folds converging to it. The bottom of the lesion was flat, showing pink-yellowish depressed areas, frequent hemorrhagic points, and deposits of friable whitish tissue of necrotic aspect. Ulceration at the proximal end of the patch, with extrusion of surgical threads, was present in two dogs. Outside the patch area, the squamocolumnar junction (Z-line) was located at its normal position in all dogs (Fig. 2).

Fig. 2.
The surgical lesion at one week (group 1): a deep edematous ulcer with necrotic bottom is seen.

Specimens obtained two weeks postoperatively (group 2 dogs) revealed clearly smaller lesions, irregularly shaped, with the denuded area located more to the gastric side. The bottom of the lesions had a brilliant and reddish aspect, covered by serosanguinous secretion, and there were converging mucosal folds around the lesions.

At four weeks postoperatively (group 3), the patch was covered by a fine and brilliant mucosa, having many smalll red points with appearance of granulation tissue. Small ulcers with extrusion of surgical thread were found in three specimens. Three specimens showed the central portion of the Z-line advancing slightly to the stomach side, suggesting invasion of the esophageal epithelium into the stomach, with return to its normal position laterally; the other three specimens had the Z-line in the anatomical position. The surrounding mucosal folds were perpendicular to the long axis of the lesion. At eight weeks postoperatively (group 4), the lesion was completely healed, as a slightly tortuous line; some areas of small scar contraction and edema could be seen, and the Z-line was at its normal site in all cases (Fig. 3). It is important to note that of the initial elliptical shape the healing evoluted to an almost linear form, indicating significant wound contraction.

Fig. 3.
Patch site at eight weeks (group 4): healed lesion and squamocolumnar junction at its anatomical position.

Optic microscopy of specimens obtained one week postoperatively (group 1 dogs) revealed complete absence of the serosa in the patch, presence of fibrinous necrotic tissue and diffuse inflammatory reaction with preserved and broken down polymorphonuclear cells. Immediately below this necrotic layer, there was granulation tissue with predominant polymorphonuclear exsudate in its outer portion, and predominance of mononuclear cells and fibroblasts in its inner portion.More deeply in the patch, the gastric muscle layers could be seen, presenting also expressive inflammatory infiltrate.The esophageal margins around the patch showed active epithelial proliferation, with mitotic basal and parabasal cells projecting towards the patch in two or more cell layers (Fig. 4). The gastric margins around the patch also exhibited epithelial proliferation, with the newly formed epithelium advancing towards the patch as an unicellular layer.

Fig. 4.
The esophageal epithelium advances from the edges of the lesion as a multicellular layer, covering the granulation tissue (first week -group 1). HE (x128).

Two weeks postoperatively (group 2), the esophagus displayed complete regeneration of the epithelium, which was pluristratified, organized, presenting papillary rudiments, and having a thickness comparable to normal adjacent epithelium. In the stomach the epithelisation was incomplete, advancing from the edges to the center as a unicellular layer with crypts (Fig. 5). In two specimens, there was spread of the esophageal epithelium into the non-epithelised gastric surface. All specimens had fibrocytes separated by small amounts of blood vessels and mononuclear cell infiltrates. Small abscesses with suture material residues, granulation tissue and polymorphonuclear cells could be seen sporadically. Connective tissue organization was more evident in the deeper layers of the lamina propria.

Fig. 5.
Migration of the gastric epithelium as unicellular layer, and initial diferentiation into crypts at the proximal border. An intense fibroblastic proliferation is seen in the lamina propria (second week - group 2). HE (x128).

At four weeks postoperatively (group 3), there was complete regeneration of the esophageal epithelium, with all its layers ( basal, spinous and granular), and initial signs of papillary formation (Fig. 6). The mucosa's lamina propria displayed connective tissue proliferation, collagen fibers, prominent interstitial angiogenesis, and significant plasma cell infiltrate. More deeply, the collagen fibers bundles were thinner and there were fewer new blood vessels. The gastric epithelium had a continuous distribution throughout, with spaced thickened areas formed by connective tissue, vascular or glandular proliferation; at this stage, the formation of crypts in all reconstituted surface indicated an evolving process of gastric epithelial glandular differentiation (Fig. 7). Three specimens showed invasion of the gastric area by esophageal epithelium underlined by an esophageal-like lamina propria.

Fig. 6.
Maturity of the stratified epithelium in the esophageal mucosa at the fourth week (group 3). HE (x128).

Fig. 7.
Newly formed gastric epithelium in the fourth week (group 3). Begining of differentiation with formation of deep crypts. HE (x128).

At eight weeks (group 4), the completely reconstituted esophageal epithelium had slightly less than normal thickness, and fewer papillae than normal; the subepithelial space showed exhuberant connective tissue, with parallel collagen fibers, some new blood vessel formation and mononuclear cell infiltrate; of considerable interest was the presence of scattered muscle fibers, arranged as thin and sometimes unicellular bundles, with appearance identical to the fibers of the muscularis mucosae. Equally complete was the gastric epithelisation, with crypts (similar to gastric glands but not wholly differentiated into glands) deepening into the subjacent connective tissue. Surgical threads were present in the scar tissue.

Fibroblastic proliferation was present in all groups, and fibrosis occurred after the second week. Foreign body reactions with giant cells and microabscesses were seen sporadically. Fibrinoid necrosis both of esophageal and gastric sections was an exclusive finding of group 1 (first week), being absent in all other groups.

The esophageal epithelium outside the operative area showed no evidence of peptic injury. Epithelial maturation was present only in the esophagus, and after the second week; the stomach did not show glandular differentiation even at eight weeks (group4), and its mucosa could not be considered mature, inspite the presence of deep crypts.

Electron microscopy of the newly formed esophageal mucosa at four weeks (group 3) displayed a fibroblast and collagen fibers rich lamina propria, and all layers usually present in a normal pluristratified epithelium: basal membrane and basal cells (Fig. 8); spinous cell with characteristic desmossomes; and granular cells layer.

Fig. 8.
Details of the esophageal mucosa in the fourth week (group 3). Fibroblast (F), basal membrane (mb), and germ layer cells (C) with nucleus (N) and nucleolus (n), (x4000).

Statistical analysis revealed continuity of the esophageal epithelium in the first week significantly different (absent) from the following weeks, and in the latter ones there was no significant difference among groups (Table I). In the stomach-1 sections, there was significantly less continuity of epithelium in the first week than in the other weeks; in the stomach-2 sections, there was significant difference of the first and second weeks when compared to the fourth and eighth weeks, without significant difference between the first and second weeks and between the fourth and eighth weeks (Table I). The esophageal and gastric epithelisation were similar in the first week, whereas in the second week esophageal epithelisation prominated; they became similar again after the fourth week.

Presence of polymorphs was significantly more pronounced in the first and second weeks, when compared to the fourth and eighth weeks; in the second week, polymorphs occurred significantly more in the stomach than in the esophagus, but they had similar occurrence in both organs in the other weeks (Table I). Mononuclear cells were present in all esophageal and gastric sections of all groups, but more proliferation was observed in the second and fourth weeks.

Fibroblastic proliferation and new vessel formation were equally present in the esophagus and stomach in all groups, except in three animals of group 4 (eight weeks), and this was not statistically significant; it is important to note that these two findings were more prominent in group 2 (two weeks). Fibrosis was observed in all gastric and esophageal sections of groups 2, 3 and 4, and in 37% of group 1, which was not statistically significant. It was observed that the later was the stage, the more intense was the fibrosis in the subepithelial space.

DISCUSSION

The dog has been the most frequently used animal in experiments of serosal patch of the gastroesophageal junction¹¹, and it was the animal chosen for the present work. In the performance of the operative procedure, an important anatomical difficulty of this animal is the presence of a short abdominal esophagus, (practically non existent on the left side, and having a length of only few millimeters on the right side), associated with a low diaphragmatic insertion. Another pertinent point was reported by BOTHA⁶, who defined that it is not possible to demonstrate a lower esophageal sphincter in this animal, and that the squamocolumnar junction is located just proximal to the cardia.

Due to anatomical characteristics of this species, previous authors frequently have used a thoracic approach for the operation^11,23,31. Contrary to this, the present study revealed that an upper abdominal midline incision, with the help of a subcostal retractor, offers an excellent exposure. The use of endotracheal tube and respirator is a must, since the esophagus has to be opened till one centimeter proximal to the squamocolumnar junction; six animals (18%) even required more proximal reinsertion of the diaphragm.

Serosal patch of the cardia in previous studies^11,30 were done using separated stitches not involving the organs cut edges. As published works have shown that continuous sutures are comparable or better than interrupted sutures in gastrointestinal anastomoses¹⁴, it was preferred to use in this experiment a one plane continuous suture involving the cut edges of the esophagus and of the stomach, which besides making the operation faster it revealed perfectly adequate to the patching technique. The finding of non obstructed and well healed anastomoses when sacrificing the animals validates the use of the technique described here. Firm adherences to the site of cardioplasty were observed in all animals and this has not been mentioned in the literature, inspite of its reported occurrence in patients reoperated on after serosal patch of the cardia¹⁸. The present study demonstrates that at the first week the patching area has changed into an ulcerated lesion with necrotic bottom, and that this lesion evolves in the second and fourth weeks with reduction in size; there is simultaneous centripetous expansion of the surrounding mucosa, and complete healing occurs by the eighth week. A contraction phenomenom has been described in serosal patches of small bowel, where the defect may be reduced to one third of its initial size , corticosteroids, systemic urogastrone and anastomotic rings have even been used to prevent this complication³³. Although miofibroblast identification techniques have not been done in the present experiment, the evolution of an initially elliptical lesion to a final linear form, clearly indicates wound contraction.

THAL²⁹ called the attention to the Z line, which always maintained its anatomical position during healing. With exception of three specimens of group 3, where the esophageal epithelium invaded the gastric side of the squamocolumnar junction, the Z line was at its anatomical position in all cases, notably in the eighth week, when healing was complete.

Upon performance of a serosal patch in the digestive tract, although the mucosa is not removed, there is solution of continuity of the epithelium and the defect is temporarily covered by serosa. The epithelisation process was described by HATAFUKU in 1964, and THAL in 1965, when they demonstrated the aplicability of serosal patch of the cardia in dogs.They reported substitution of the serosa by granulation tissue one week after the patching, with angiogenesis derived from the seromuscular layer of the gastric wall; in a subsequent stage, there was rapid proliferation of the squamous epithelium on the esophageal side, and of the columnar epithelium on the gastric side. Similarly to these findings, all specimens obtained at one week (group 1), both in the esophageal and gastric sections, revealed disappearance of the serosa, which was replaced by granulation tissue with intense new vessel formation. Fibrinoid necrosis and rich inflammatory infiltrate with predominance of polymorphonuclear cells occurred also; more deeply, there was fibroblastic activity.

Begining of re-epithelisation was seen in all one week specimens, as unicellular epithelium in the stomach and pluricellular epithelium in the esophagus. The injured epithelial tissue usually reacts in well defined steps, which sequentially involve cellular mobilization, migration, proliferation and differentiation; they are engendered in such a way that the epithelial regeneration progresses from the edges to the center of the lesion. This occurs with little variation both in the esophagus and in the stomach²².

The findings suggest that the serosa and the underlying muscular layer of the patch were subjected to severe aggression by exposure to digestive juice, which led to fibrinoid necrosis accompanied by its inflammatory component. Concomitant granulation tissue with intense angiogenesis was formed, and served as bed for the begining of epithelial regeneration. The typically inflammatory changes justify the macroscopic appearance of the patch at this stage, as a deep edematous ulcer with irregular edges and a necrotic base.

With reference to the time required by the newly formed mucosa to cover the defect, THAL²⁹, reported it as five weeks for the cardia. For the duodenum, KOBOLD¹⁵ cited three to four weeks. HIROTA¹³ described a period of eight weeks for complete epithelisation of the gastric antrum, and of six weeks for the small bowel. VINHAES ³⁴ detected fully epithelised antro-pyloric patches of dogs at eight weeks.

Complete epithelisation of the esophageal segment was found in all animals sacrificed at two weeks (group 2), with the epithelium considered mature, in view of the appearance of the epithelial layers and of presence of papillae rudiments. At the stomach, this group showed complete epithelisation only in 25% of the examined sections, whereas all specimens of group 3 (fourth week) were fully epithelised, displaying crypts but no glands. These statistically significant findings led to the inference that in serosal patches of the cardia, the epithelisation process occurs at a faster speed in the esophagus than in the stomach.

POLLARA²³ demonstrated that in the re-epithelisation of the GE junction under gastroesophageal reflux conditions, the gastric mucosa exhibits a tendency to invade the esophagus. It is of considerable interest that in the present experiment the esophageal mucosa around the patch did not exhibit any inflammatory change that could be ascribed to reflux and that invasion of the gastric side of the Z line by esophageal mucosa occurred in two animals of Group 2 and in three animals of Group 3; this gives evidence that in serosal patches, where faster esophageal epithelisation seems to occur, the esophageal epithelium has a tendency to invade the gastric side of the Z line, during the proliferative phase (two to four weeks), differently of what was reported by Pollara under severe gastroesophageal reflux. Nevertheless, at eight weeks, when epithelial healing was complete, all specimens had squamocolumnar junction at the anatomical position, which demonstrates that at a later stage both epithelia have a tendency to respect their limits.

At the end of the experiment, the esophageal epithelium was histologically mature, whereas the gastric epithelium had deep crypts simulating glands without parietal or chief cells. The evolution of the gastric epithelium from a unicellular layer to shallow crypts, and later to deep crypts simulating glands, suggests that the observation time may have been shorter than the time required for total gland differentiation.

The subepithelial space or lamina propria was studied in the patching of the duodenum by KOBOLD¹⁵, and of the cardia by THAL³¹ : they demonstrated abundant inflammatory and fibroblastic activity in the first week, and little activity in the eighth week. At the first week, the present findings were similar to these reports, although the fact that called more attention was the extensive fibrinoid necrosis, present in all gastric and esophageal sections and associated to massive presence of polymorphonuclear cells. At the second week, polymorphs predominated in the yet non epithelised stomach, whereas mononuclear cells predominated in the already epithelised esophagus. At the fourth and eighth weeks, the presence of polymorphs was irrelevant, indicating that these cells predominate while the surface of the patch is uncovered by epithelium. Fibroblastic and mononuclear proliferation were more intense in the second and fourth weeks, and fibrosis started in the second week, becoming more pronounced after the fourth week.

The evolution of healing of the lamina propria can be divided into three stages: inflammatory, which reaches the second week; fibroblastic proliferative, with its peak in the fourth week; and fibroplastic, between the fourth and eight weeks. Although similar to general healing processes, the progression of these stages was slower in the serosal patches; this may be justified by the hostile environment offered by the digestive lumen, by the presence of foreign body reactions with granulomas and giant cells around suture threads, and by infective foci such as microabscesses.

The capacity of smooth muscle to regenerate has been previously described²². At eight weeks, smooth muscle bundles (sometimes unicellular) were encountered amidst the lamina propria healing area; they were located in continuity with the muscularis mucosae, and their presence constitutes evidence of smooth muscle regeneration.

With reference to the electron microscopy, there is no literature report of ultrastructural studies of newly formed epithelium in serosal patches. The optical microscopy suggested maturity of the newly formed esophageal epithelium and the transmission electron microscopy study done at the fourth week confirmed it, revealing presence of all layers which normally compose stratified epithelia, which are: basal cells, spinous cells and granular cells, with a fibroblast and collagen rich subepithelial space. The ultrastructural study was not done in the stomach, since optic microscopy revealed presence only of mucus secreting cells, which are cells primarily involved in repair processes.

It has been reported in the literature that inspite satisfactory results, clinical use of serosal patches of the cardia has always been followed by small but persistent number of failures in 7 to 15% of patients, notably as postoperative stenoses^{2,3,12,17,18,26,30,32}. This may be of serious consequence to patients, since patching of the cardia is used justly to widen the narrowed lumen at the gastro- esophageal junction.

According THOMPSON³³ the occurrence of stenosis would be related to wound contraction following section of the muscle layer of the organ: it would be aggravated by slow re-epithelisation and it could reduce the patched area to one third of its initial size and suggested as yet that the contraction could be inhibited by systemic urogastrone, corticosteroids and supporting anastomotic rings.

Although stenoses weren't seen in the present study, attention is called to occurrence of a relatively slow epithelial repair process, to an intense initial inflammatory response, to an abundant connective tissue proliferation, and to the evolutive macroscopic aspect suggesting wound contraction. These observations strongly support a need for further experiments attempting to facilitate the repair process, by stimulating re-epithelisation and inhibiting wound contraction, in order to improve the results of the patching techniques.

CONCLUSIONS

The following conclusions can be drawn from the experimental studies undertaken:

1. the serosa disappears at the initial stage of repair;

2. the epithelisation progresses from the edges to the center of the lesion, being pluricellular in the esophagus and unicellular in the stomach;

3. the esophageal epithelisation is faster than the gastric epithelisation, and both are complete at the first and fourth weeks, respectively;

4. the mucosa's lamina propria evolves through three phases: inflammation, fibroblast proliferation and fibrosis;

5. there is smooth muscle regeneration at late stages of repair;

6. at conclusion of healing, the squamocolumnar junction maintains its anatomical position;

7. all ultrastructural layers of normal epithelium are present in the newly formed esophageal epithelium.

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MENDELSSONH, P.; MAGALHÃES, A.; GOLDENBERG, S. - Tamponamento seroso da junção esofagogástrica: estudo experimental em cães. Acta Cir. Bras., 13(3):00-00, 1998.

RESUMO: Trinta e dois cães foram submetidos ao tamponamento seroso da junção esofagogástrica, com o objetivo de investigar experimentalmente o processo de reparação mucosa. A operação constou de cardiotomia, interessando um centímetro do esôfago e dois centímetros do estômago. Esta secção foi obliterada pelo fundo gástrico, originando uma superfície serosa elíptica, voltada para o lúmen, com três centímetros de comprimento por um centímetro de maior largura. Os animais foram divididos em quatro grupos de oito cães cada (Grupos: 1, 2, 3 e 4), sacrificados após uma, duas, quatro e oito semanas respectivamente. Os resultados foram avaliados quanto aos aspectos clínicos, pós-operatórios, e da análise macro e microscopicas dos espécimes obtidos. A evolução pós-operatória mostrou pequena morbidade, sem sinais de obstrução do trato digestivo. Ficou demonstrado à macroscopia, que a área do tamponamento exibe, na primeira semana, aspecto de lesão ulcerada, com fundo necrótico; na segunda e quarta semanas houve redução da área cruenta, até a completa cicatrização, melhor observada na oitava semana. À microscopia, a membrana serosa desapareceu precocemente, dando lugar a infiltrado inflamatório com intensa neoformação vascular, que serviu de leito para a proliferação epitelial.A neoepitelização fez-se das bordas para o centro da lesão. No esôfago, em camadas pluricelulares, completou-se em duas semanas, e no estômago, com epitélio unicelular estava completa na quarta semana.

DESCRITORES: Cirurgia gastrointestinal. Epitélio.

ACKNOWLEDGEMENTS:

The authors are grateful to Prof. Neil F. Novo and Yara Juliano for the statistical anlysis, to Prof. A. Barichello for the text revision and to Fundação de Apoio à Pesquisa do Distrito Federal for the financial support.

Address for correspondence:

Paulo Mendelssonh

SQN 205, Bloco G, Apto 103

Asa Norte, Brasília, DF. 70843-070

Fone: [phone]

Accepted for publication march, 1998.

1. Work performed at the Curso de Pós Graduação em Técnica Operatório e Cirurgia Experimental da Universidade Federal de São Paulo.

Work performed at the Curso de Pós Graduação em Técnica Operatório e Cirurgia Experimental da Universidade Federal de São Paulo.

2. Professor of Surgery at the University of Brasilia.

3. Professor of Pathology at the University of Brasília

4. Professor of Surgery at the Federal University of São Paulo.

Datas de Publicação

• Publicação nesta coleção
  19 Nov 1998
• Data do Fascículo
  Jul 1998

Histórico

• Aceito
  Mar 1998